Prostaglandins play a major role in the inflammation process. The inhibition of prostaglandin production, especially production of PGG.sub.2, PGH.sub.2 and PGE.sub.2, has been a common target of antiinflammatory drug discovery. Non-steroidal antiinflammatory drugs (NSAID's) have been found to prevent the production of prostaglandin-induced pain and swelling associated with the inflammation process by inhibiting enzymes in the human arachidonic acid/prostaglandin pathway, including the enzyme cyclooxygenase (now identified as COX-1). Recently, the sequence of another heretofore unknown enzyme in the human arachidonic acid/prostaglandin pathway has been reported by T. Hla and K. Nielson, Proc. Natl. Acad. Sci, USA, 89, 7384 (1992) and named "cyclooxygenase-2 (COX-2)" or "prostaglandin G/H synthase II". The expression of COX-2 is readily induced in response to pro-inflammatory stimuli in cells in vivo, including macrophages, monocytes, synovial cells and endothelial cells. Cyclooxygenase-2 is inducible by cytokines or endotoxins and such induction is inhibited by glucocortoids (J. Masferrer et al., Proc. Natl. Acad. Sci, USA, 89, 3917 (1992)).
The biological importance and distribution of cyclooxygenase isoforms is becoming known. It has been observed that COX-2 is induced in parallel with the development of inflammation and prostaglandin production in common inflammation and arthritis models. COX-2 expression also has been observed in cancer cells, such as colorectal cancer (H. Sano et al, Cancer Res., 55, 3785-9 (1995)).
Various compounds have been described as COX-2 inhibitors. S. Bertenshaw describes thiophene compounds which selectively inhibit COX-2 [Biomed. and Med. Chem. Lett., 5, 2919-22 (1995)]. H. Huang et al. [J. Med. Chem., 39, 253-66 (1996)] describe diarylspiro[2.4]heptenes as highly selective COX-2 inhibitors. J. Li et al. [J. Med. Chem., 38, 4570-78 (1995)] describe diarylcyclopentenes as highly selective COX-2 inhibitors. J. Li et al. [J. Med. Chem., 39, 1846-56 (1996)] describe terphenyl compounds as highly selective COX-2 inhibitors.
Compounds which selectively inhibit cyclooxygenase-2 have been described in U.S. Pat. Nos. 5,393,790, 5,474,995 and WO documents WO94/15932, WO94/27980, WO95/00501, WO94/13635, WO94/20480, WO95/11883, WO95/05395, WO95/15316, WO96/03388, WO96/03387 and WO94/26731.
The use of nuclear medicine and nuclear magnetic resonance, including X-ray, NMR and MRI, has been described for analyzing tissue, especially bone and soft tissue, such as cartilage, synovium and organs.
Positron-emission tomography (PET) also has been used for visualizing a patient's condition. In PET, compounds labeled with positron-emitting radioisotopes are administered to a patient and detected so as to quantify the distribution of radioactivity. Common radioisotopes found useful in PET include .sup.11 C, .sup.15 O, .sup.13 N, .sup.18 F, .sup.62 Cu and .sup.64 Cu, especially where incorporated in perfusion agents, metabolism agents, receptor-based radiopharmaceuticals and receptor-based systems [T. McCarthy et al., J. Chem. Ed., 71, 830-36 (1994)].
Various methods have been used to image inflanmmatory responses and conditions. Indium-111 labeled neutrophils have been described in imaging the inflammatory response to myocardial infarctions [Br. Heart J., 57, 23 (1987)].
2-Deoxy-2-(.sup.18 F)fluoro-D-glucose (FDG) is one of the more established metabolism agents for detecting inflammation by positron tomography. It has been used to measure pulmonary inflammation [Acta. Radio. Supp., 376, 148 (1991). It has also been described for use in diagnosing the presence of tumors [Ophthalmic. Res., 18, 292 (1986)].
The synthesis and in vivo distribution of .sup.18 F-flurbiprofen was described by Stewart Todd [Dissertation Abstracts. Int., 52, 2566-B (1991)]. However, fluribiorofen is non-selective as it inhibits both COX-1 and COX-2, and PET analysis would present a high background during in vivo analysis due to COX-1 detection.
Although the use of radiation emitting pharmaceuticals has proven useful in non-invasive imaging, there still exists a need for more selective non-invasive diagnostic techniques to identify early detection of disease, such as arthritis, CNS-disorders and injuries, and neoplasia, as well as monitoring effectiveness of treatment.